The retention behavior and lipophilicity of aripiprazole and its nine impurities as well as ziprasidone and its five impurities have been examined by thin-layer chromatography using RP-18 stationary phase and different mixtures of methanol, water, and ammonia; and ethanol, water, and ammonia as the mobile phases. In both examined chromatographic systems, linear relationships were established between retention parameters and the volume fraction of the methanol and ethanol in mobile phase (r > 0.948 for methanol and r > 0.971 for ethanol). Correlation matrices obtained between experimentally obtained lipophilicity indices (RM0, m, and C0) and calculated log P values showed that, for the examined antipsychotics and their impurities, RM0 and m values are more reliable lipophilicity parameters compared to C0 values. In addition, the performed principal component analysis (PCA) has provided new information about the similarity and differences between the tested compounds as well as the experimental lipophilicity indices and calculated log P values. The experimentally obtained RM0 values and the computed molecular parameters of the examined compounds were further used for the quantitative structure—retention relationship (QSRR) study in order to determine the most important properties governing retention. The QSRR modeling was performed by use of the partial least squares regression, and predictive performances of the developed QSRR models were tested by use of the cross-validation and external test set prediction. The obtained results revealed that, apart from lipophilicity, topological descriptors and molecular weights of the tested compounds have the strongest influence on the retention behavior of the examined antipsychotics and their impurities in reversed-phase thin-layer chromatography. The predictive performance of the developed QSRR model suggests its applicability for a reliable prediction of the retention behavior of the congeners.
T.L.Lemke, D.A.Williams, V.F.Roche, S.W.Zito, Foye’s Principles of Medicinal Chemistry, 7th edn., Lippincott Williams & Wilkins, Baltimore, MD, 2012, 449–484.
T.L.Lemke, D.A.Williams, V.F.Roche, S.W.Zito, Foye’s Principles of Medicinal Chemistry, 7th edn., Lippincott Williams & Wilkins, Baltimore, MD, 2012, 449–484.)| false